The objective of these studies is to elucidate the biochemical mechanisms of chemical toxicity. Presently we are focusing on the pulmonary toxicity of some important environmental organohalogen compounds. Some of the toxic agents being investigated in our laboratory are carcinogenic, while others are non-carcinogenic. Some of the compounds under investigation are trichloroethylene, bis (chloromethyl) ether and 2-chloroethanol. Our approach to the study of the mechanism of pulmonary toxicity of organohalogens is three-fold. (1) Biochemical changes in the specific activities of several lung enzymes are sought and these changes constitute markers for early indices of injury caused by exposure to chemicals. (2) Animals are treated with drugs which are known to modify the activites of drug metabolizing enzymes in the lung or liver (but have no effect on the enzymes used as markers) and the relationships between enzyme activities, accumulation of intermediates and histopathological changes in the target organ following exposure to the agent are studied. (3) The in vivo and in vitro effects of the different metabolites (intermediates) on enzymes markers in various subcellular fractions are studied in order to show a direct relationship between the site of toxic action and the proposed intermediate.